tbuckley/cabot-search huggingface dataset:
Blockade of neutrophil recruitment to tumor sites based on sialic acid-modified nanoplatforms enhances the efficacy of checkpoint blockade immunotherapy
Authors: Meng Chen, Zhaowei Qi, Xianmin Meng, Shuo Wang, Xueying Zheng, Miao Hu, Xinrong Liu, Yanzhi Song, Yihui Deng
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Checkpoint inhibitors are designed to rejuvenate depleted or suppressed T cells in the tumor microenvironment, relying on the immune system to control and kill tumors. However, accumulating evidence indicates that tumor-infiltrating neutrophils impede the proliferation and activation of T cells and determine the resistance to checkpoint blockade and chemotherapy. In this study, sialic acid ligand-modified colchicine derivative phospholipid complexes specifically targeted tumor-associated neutrophils in the peripheral blood, blocked neutrophil accumulation in tumors, and attenuated the inhibitory effect of infiltrating neutrophils on T cells. Neutrophil blocking therapy enhanced the immunotherapy effect of the PD-L1 antibody in S180 advanced tumors and 4T1 breast cancer. Our study found that PD-L1 antibody monotherapy increased the tumor infiltration of immunosuppressive neutrophils. Combination therapy with neutrophil blocking can greatly reduce tumor-infiltrating neutrophils and increase the proliferation of cytotoxic CD8+ T lymphocytes in the tumor. The combination therapy significantly improved the survival rate of mice with advanced S180 tumors and increased the sensitivity of immune checkpoint inhibitors to 4T1 cold tumors.
Home telemonitoring versus hospital care in complicated pregnancies in the Netherlands: a randomised, controlled non-inferiority trial (HoTeL)
Authors: Mireille N Bekker, Maria P H Koster, Willem R Keusters, Wessel Ganzevoort, Jiska M de Haan-Jebbink, Koen L Deurloo, Laura Seeber, David P van der Ham, Nicolaas P A Zuithoff, Geert W J Frederix, Josephus F M van den Heuvel, Arie Franx
Journal: The Lancet Digital Health (2023)

Women with complicated pregnancies often require hospital admission. Telemonitoring at home is a promising alternative that fulfils a worldwide need in obstetric health care. Moreover, the COVID-19 pandemic has accelerated the transformation to digital care. The aim of this study was to evaluate safety, clinical effectiveness, patient satisfaction, and costs of home telemonitoring against hospital care in complicated pregnancies.
Effectiveness, reach, uptake, and feasibility of digital health interventions for adults with hypertension: a systematic review and meta-analysis of randomised controlled trials
Authors: George Siopis, George Moschonis, Evette Eweka, Jenny Jung, Dominika Kwasnicka, Bernard Yeboah-Asiamah Asare, Vimarsha Kodithuwakku, Ruben Willems, Nick Verhaeghe, Lieven Annemans, Rajesh Vedanthan, Brian Oldenburg, Yannis Manios, Brian Oldenburg, Dominika Kwasnicka, Enying Gong, Jenny Jung, Bernard Yeboah-Asiamah Asare, Vimarsha Kodithuwakku, Konstantinos Votis, Sofia Segkouli, Andreas Triantafyllidis, Odysseas Kyparissis, Ioannis Paliokas, Eleftheria Polychroniou, Lieven Annemans, Nick Verhaeghe, Ruben Willems, Dirk De Craemer, Yannis Manios, Kostas Anastasiou, Konstantinos Tserpes, Christina Mavrogianni, Eva Karaglani, Electra Kalogerakou, Maria Maragkoudaki, Agathi Ntzouvani, Katerina Kontochristopoulou, Sabine Dupont, Elizabeth Dupont, Leo Dauzon, Maartje Roskams, Niamh Lennox-Chhugani, Martin Perrin, Niamh Daly Day, Georgina Ferrer, Orla Snook, Edelweiss Aldasoro, Alejandro Gil-Salmerón, Pilar Gangas Peiró, Darren Curran, Fiona Lyne, Nereide A. Curreri, George Moschonis, George Siopis, Nazzareno Pierantozzi, Claudia D'Antonio, Giacomo Vespasiani, Teresa Almonti, Helen Skouteris, Tracy Taylor, Melissa Savaglio, Konstantinos Makrilakis, George Stergiou, Stavros Liatis, George Karamanakos, Chrysi Koliaki, Anastasios Kollias, Eva Zikou, Haris Dimosthenopoulos, Rajesh Vedanthan, Keng-Yen Huang, Samrachana Adhikari, Kun Qian, Julia Dickhaus, Kimberly Carney, Evette Eweka, Farhan Sahito, Dusan Pavlovic, Djordje Djokic, Arzoo Sahito, Gisella Battalova, Chiara Seghieri, Sabina Nutti, Milena Vanieri, Nicola Belle, Gaia Bertarelli, Paola Cantarelli, Francesca Ferre, Anna Noci, Constanza Tortu, Nadia Bozzi, Dina Ferrari, Rachele Borelli, Violeta Iotova, Yoto Yotov, Natalia Usheva, Anna Kozhuharova, Vanya Russeva, Vanya Marinova, Sonya Koleva, Virginia Atanasova, Tanya Stefanova, Kaloyan Tsochev, Luis Moreno Aznar, Rosa Magallón Botaya, Gloria Bueno Lozano, Pilar De Miguel-Etayo, Esther Ma Gonzalez-Gil, María L. Miguel-Berges, Susana Pérez, Bárbara Oliván Blázquez, Natalia Giménez-Legarre, Florian Toti, Skerdi Prifti, Blerina Bombaj, Ditila Doracaj, Ornela Laze, Adriana Lapardhaja, Luftime Bruka
Journal: The Lancet Digital Health (2023)

Digital health interventions are effective for hypertension self-management, but a comparison of the effectiveness and implementation of the different modes of interventions is not currently available. This study aimed to compare the effectiveness of SMS, smartphone application, and website interventions on improving blood pressure in adults with hypertension, and to report on their reach, uptake, and feasibility.
Embedding patient-reported outcomes at the heart of artificial intelligence health-care technologies
Authors: Samantha Cruz Rivera, Xiaoxuan Liu, Sarah E Hughes, Helen Dunster, Elaine Manna, Alastair K Denniston, Melanie J Calvert
Journal: The Lancet Digital Health (2023)

Integration of patient-reported outcome measures (PROMs) in artificial intelligence (AI) studies is a critical part of the humanisation of AI for health. It allows AI technologies to incorporate patients' own views of their symptoms and predict outcomes, reflecting a more holistic picture of health and wellbeing and ultimately helping patients and clinicians to make the best health-care decisions together. By positioning patient-reported outcomes (PROs) as a model input or output we propose a framework to embed PROMs within the function and evaluation of AI health care. However, the integration of PROs in AI systems presents several challenges. These challenges include (1) fragmentation of PRO data collection; (2) validation of AI systems trained and validated against clinician performance, rather than outcome data; (3) scarcity of large-scale PRO datasets; (4) inadequate selection of PROMs for the target population and inadequate infrastructure for collecting PROs; and (5) clinicians might not recognise the value of PROs and therefore not prioritise their adoption; and (6) studies involving PRO or AI frequently present suboptimal design. Notwithstanding these challenges, we propose considerations for the inclusion of PROs in AI health-care technologies to avoid promoting survival at the expense of wellbeing.
Comment on Serés-Noriega et al. Use of the Steno T1 Risk Engine Identifies Preclinical Atherosclerosis Better Than Use of ESC/EASD-2019 in Adult Subjects With Type 1 Diabetes at High Risk. Diabetes Care 2022;45:2412–2421
Authors: José-Miguel González-Clemente, Gemma Llauradó, Albert Cano, Olga Giménez-Palop, Lara Albert, Joan Vendrell
Journal: Diabetes Care (2023)
Prevalence of CFTR variants in primary immunodeficiency patients with bronchiectasis is an important modifying cofactor
Authors: Dylan Lawless, Hana Lango Allen, James E.D. Thaventhiran, Sarah Goddard, Oliver S. Burren, Evie Robson, Daniel Peckham, Kenneth G.C. Smith, Sinisa Savic
Journal: Journal of Allergy and Clinical Immunology (2023)

BackgroundCystic fibrosis (CF) is one of the most common life-limiting autosomal-recessive disorders and is caused by genetic defects in the CF transmembrane conductance regulator (CFTR) gene. Some of the features of this multisystem disease can be present in primary immunodeficiency (PID).ObjectiveWe hypothesized that a carrier CFTR status might be associated with worse outcome regarding structural lung disease in patients with PID.MethodsA within-cohort and population-level statistical genomic analysis of a large European cohort of PID patients was performed using genome sequence data. Genomic analysis of variant pathogenicity was performed.ResultsCompared to the general population, p.Phe508del carriage was enriched in lung-related PID. Additionally, carriage of several pathogenic CFTR gene variants were increased in PID associated with structural lung damage compared to PID patients without the structural lung damage. We identified 3 additional biallelic cases, including several variants not traditionally considered to cause CF.ConclusionGenome sequencing identified cases of CFTR dysfunction in PID, driving an increased susceptibility to infection. Large national genomic services provide an opportunity for precision medicine by interpreting subtle features of genomic diversity when treating traditional Mendelian disorders. Cystic fibrosis (CF) is one of the most common life-limiting autosomal-recessive disorders and is caused by genetic defects in the CF transmembrane conductance regulator (CFTR) gene. Some of the features of this multisystem disease can be present in primary immunodeficiency (PID). We hypothesized that a carrier CFTR status might be associated with worse outcome regarding structural lung disease in patients with PID. A within-cohort and population-level statistical genomic analysis of a large European cohort of PID patients was performed using genome sequence data. Genomic analysis of variant pathogenicity was performed. Compared to the general population, p.Phe508del carriage was enriched in lung-related PID. Additionally, carriage of several pathogenic CFTR gene variants were increased in PID associated with structural lung damage compared to PID patients without the structural lung damage. We identified 3 additional biallelic cases, including several variants not traditionally considered to cause CF. Genome sequencing identified cases of CFTR dysfunction in PID, driving an increased susceptibility to infection. Large national genomic services provide an opportunity for precision medicine by interpreting subtle features of genomic diversity when treating traditional Mendelian disorders.
Clonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy
Authors: Ramona A. Hoh, Linnea Thörnqvist, Fan Yang, Magdalena Godzwon, Jasmine J. King, Ji-Yeun Lee, Lennart Greiff, Scott D. Boyd, Mats Ohlin
Journal: Journal of Allergy and Clinical Immunology (2023)

Allergic disease reflects specific inflammatory processes initiated by interaction between allergen and allergen-specific IgE. Specific immunotherapy (SIT) is an effective long-term treatment option, but the mechanisms by which SIT provides desensitization are not well understood.
Stratum corneum lipid and cytokine biomarkers at age 2 months predict the future onset of atopic dermatitis
Authors: Evgeny Berdyshev, Jihyun Kim, Byung Eui Kim, Elena Goleva, Taras Lyubchenko, Irina Bronova, Anna Sofia Bronoff, Olivia Xiao, Jiwon Kim, Sukyung Kim, Mijeong Kwon, Sungjoo Lee, Yu Jeong Seo, Kyunga Kim, Suk-Joo Choi, Soo-Young Oh, Seung Hwan Kim, So Yeon Yu, Seung Yong Hwang, Kangmo Ahn, Donald Y.M. Leung
Journal: Journal of Allergy and Clinical Immunology (2023)
Nano-enabled agglomerates and compact: Design aspects of challenges
Authors: Nazurah Binti Sazali, Lai Wah Chan, Tin Wui Wong
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Nanoscale medicine confers passive and active targeting potential. The development of nanomedicine is however met with processing, handling and administration hurdles. Excessive solid nanoparticle aggregation and caking result in low product yield, poor particle flowability and inefficient drug administration. These are overcome by converting the nanoparticles into a microscale dosage form via agglomeration or compaction techniques. Agglomeration and compaction nonetheless predispose the nanoparticles to risks of losing their nanogeometry, surface composition or chemistry being altered and negating biological performance. This study reviews risk factors faced during agglomeration and compaction that could result in these changes to nanoparticles. The potential risk factors pertain to materials choice in nanoparticle and microscale dosage form development, and their interplay effects with process temperature, physical forces and environmental stresses. To render the physicochemical and biological behaviour of the nanoparticles unaffected by agglomeration or compaction, modes to modulate the interplay effects of material and formulation with processing and environment variables are discussed.
Nasal allergen challenge (NAC): Practical aspects and applications from an EU/US perspective—a Work Group Report of the AAAAI Rhinitis, Rhinosinusitis and Ocular Allergy Committee
Authors: Seong H. Cho, Anil Nanda, Anjeni Keswani, Allen Adinoff, Fuad M. Baroody, Jonathan A. Bernstein, Alina Gherasim, Joseph K. Han, Jerald W. Koepke, Dennis K. Ledford, Amber N. Pepper, Carmen Rondón, Amy Schiffman, Martin Wagenmann, Paloma Campo
Journal: Journal of Allergy and Clinical Immunology (2023)
Human gene-engineered calreticulin mutant stem cells recapitulate MPN hallmarks and identify targetable vulnerabilities
Authors: Johannes Foßelteder, Gabriel Pabst, Tommaso Sconocchia, Angelika Schlacher, Lisa Auinger, Karl Kashofer, Christine Beham-Schmid, Slave Trajanoski, Claudia Waskow, Wolfgang Schöll, Heinz Sill, Armin Zebisch, Albert Wölfler, Daniel Thomas, Andreas Reinisch
Journal: Leukemia (2023)

Abstract Calreticulin ( CALR ) mutations present the main oncogenic drivers in JAK2 wildtype (WT) myeloproliferative neoplasms (MPN), including essential thrombocythemia and myelofibrosis, where mutant (MUT) CALR is increasingly recognized as a suitable mutation-specific drug target. However, our current understanding of its mechanism-of-action is derived from mouse models or immortalized cell lines, where cross-species differences, ectopic over-expression and lack of disease penetrance are hampering translational research. Here, we describe the first human gene-engineered model of CALR MUT MPN using a CRISPR/Cas9 and adeno-associated viral vector-mediated knock-in strategy in primary human hematopoietic stem and progenitor cells (HSPCs) to establish a reproducible and trackable phenotype in vitro and in xenografted mice. Our humanized model recapitulates many disease hallmarks: thrombopoietin-independent megakaryopoiesis, myeloid-lineage skewing, splenomegaly, bone marrow fibrosis, and expansion of megakaryocyte-primed CD41 + progenitors. Strikingly, introduction of CALR mutations enforced early reprogramming of human HSPCs and the induction of an endoplasmic reticulum stress response. The observed compensatory upregulation of chaperones revealed novel mutation-specific vulnerabilities with preferential sensitivity of CALR mutant cells to inhibition of the BiP chaperone and the proteasome. Overall, our humanized model improves purely murine models and provides a readily usable basis for testing of novel therapeutic strategies in a human setting.
Posttraumatic Stress Symptoms in Patients With Cancer During the COVID-19 Pandemic: A One-Year Longitudinal Study
Authors: Etienne Bastien, Sophie Lefèvre-Arbogast, Justine Lequesne, François Gernier, François Cherifi, Olivier Rigal, Lydia Guittet, Jean‐Michel Grellard, Giulia Binarelli, Marie Lange, Marie Fernette, Laure Tron, Adeline Morel, Doriane Richard, Bénédicte Griffon, Alexandra Leconte, Florian Quilan, Louis-Ferdinand Pépin, Fabrice Jardin, Marianne Leheurteur, Audrey Faveyrial, Bénédicte Clarisse, Florence Joly
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Patients with cancer may be particularly vulnerable to psychological consequences of the COVID-19 pandemic. We studied the prevalence and evolution of posttraumatic stress symptoms (PTSS) in patients with cancer during the pandemic waves, and we investigated factors associated with high symptoms. Methods: COVIPACT is a 1-year longitudinal prospective study of French patients with solid/hematologic malignancies receiving treatment during the first nationwide lockdown. PTSS were measured every 3 months from April 2020 using the Impact of Event Scale–Revised. Patients also completed questionnaires on their quality of life, cognitive complaints, insomnia, and COVID-19 lockdown experience. Results: Longitudinal analyses involved 386 patients with at least one PTSS assessment after baseline (median age, 63 years; 76% female). Among them, 21.5% had moderate/severe PTSS during the first lockdown. The rate of patients reporting PTSS decreased at lockdown release (13.6%), increased again at second lockdown (23.2%), and slightly declined from the second release period (22.7%) to the third lockdown (17.5%). Patients were grouped into 3 trajectories of evolution. Most patients had stable low symptoms throughout the period, 6% had high baseline symptoms slowly decreasing over time, and 17.6% had moderate symptoms worsening during the second lockdown. Female sex, feeling socially isolated, worrying about COVID-19 infection, and using psychotropic drugs were associated with PTSS. PTSS were associated with impaired quality of life, sleep, and cognition. Conclusions: Approximately one-fourth of patients with cancer experienced high and persistent PTSS over the first year of the COVID-19 pandemic and may benefit from psychological support. ClinicalTrials.gov identifier: NCT04366154
Speciation Underpinned by Unexpected Molecular Diversity in the Mycorrhizal Fungal Genus<i>Pisolithus</i>
Authors: Plett, Jonathan M., Miyauchi, Shingo, Morin, Emmanuelle, Plett, Krista, Wong-Bajracharya, Johanna, de Freitas Pereira, Maira, Kuo, Alan, Henrissat, Bernard, Drula, Elodie, Wojtalewicz, Dominika, Riley, Robert, Pangilinan, Jasmyn, Andreopoulos, William, LaButti, Kurt, Daum, Chris, Yoshinaga, Yuko, Fauchery, Laure, Ng, Vivian, Lipzen, Anna, Barry, Kerrie, Singan, Vasanth, Guo, Jie, Lebel, Teresa, Costa, Mauricio Dutra, Grigoriev, Igor V., Martin, Francis, Anderson, Ian C., Kohler, Annegret
Journal: Molecular Biology and Evolution (2023)

Abstract The mutualistic ectomycorrhizal (ECM) fungal genus Pisolithus comprises 19 species defined to date which colonize the roots of &amp;gt;50 hosts worldwide suggesting that substantial genomic and functional evolution occurred during speciation. To better understand this intra-genus variation, we undertook a comparative multi-omic study of nine Pisolithus species sampled from North America, South America, Asia, and Australasia. We found that there was a small core set of genes common to all species (13%), and that these genes were more likely to be significantly regulated during symbiosis with a host than accessory or species-specific genes. Thus, the genetic “toolbox” foundational to the symbiotic lifestyle in this genus is small. Transposable elements were located significantly closer to gene classes including effector-like small secreted proteins (SSPs). Poorly conserved SSPs were more likely to be induced by symbiosis, suggesting that they may be a class of protein that tune host specificity. The Pisolithus gene repertoire is characterized by divergent CAZyme profiles when compared with other fungi, both symbiotic and saprotrophic. This was driven by differences in enzymes associated with symbiotic sugar processing, although metabolomic analysis suggest that neither copy number nor expression of these genes is sufficient to predict sugar capture from a host plant or its metabolism in fungal hyphae. Our results demonstrate that intra-genus genomic and functional diversity within ECM fungi is greater than previously thought, underlining the importance of continued comparative studies within the fungal tree of life to refine our focus on pathways and evolutionary processes foundational to this symbiotic lifestyle.
circFNDC3B Accelerates Vasculature Formation and Metastasis in Oral Squamous Cell Carcinoma
Authors: Xiang Li, Chenxing Wang, Hang Zhang, Yangjie Li, Deqiang Hou, Dingshan Liu, Rongyao Xu, Jie Cheng, Laikui Liu, Yu Fu, Jinhai Ye, Hongbing Jiang
Journal: Cancer Research (2023)

Abstract Emerging evidence has demonstrated that circular RNAs (circRNA) are involved in cancer metastasis. Further elucidation of the role of circRNAs in oral squamous cell carcinoma (OSCC) could provide insights into mechanisms driving metastasis and potential therapeutic targets. Here, we identify a circRNA, circFNDC3B, that is significantly upregulated in OSCC and is positively associated with lymph node (LN) metastasis. In vitro and in vivo functional assays showed that circFNDC3B accelerated the migration and invasion of OSCC cells and the tube-forming capacity of human umbilical vein endothelial cells and human lymphatic endothelial cells. Mechanistically, circFNDC3B regulated ubiquitylation of the RNA-binding protein FUS and the deubiquitylation of HIF1A through the E3 ligase MDM2 to promote VEGFA transcription, thereby enhancing angiogenesis. Meanwhile, circFNDC3B sequestered miR-181c-5p to upregulate SERPINE1 and PROX1, which drove epithelial–mesenchymal transition (EMT) or partial-EMT (p-EMT) in OSCC cells and promoted lymphangiogenesis to accelerate LN metastasis. Overall, these findings uncovered the mechanistic role of circFNDC3B in orchestrating cancer cell metastatic properties and vasculature formation, suggesting circFNDC3B could be a potential target to reduce OSCC metastasis. Significance: Dual functions of circFNDC3B in enhancing the metastatic ability of cancer cells and promoting vasculature formation through regulation of multiple pro-oncogenic signaling pathways drive lymph node metastasis of OSCC.
Single Dose of Antibiotic Reduced Maternal Sepsis
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Federal Officials Issue Initial Guidance to Rein in Drug Spending
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal